We propose to examine the response of a transplantable rat mammary adenocarcinoma and critical host tissues to specific antitumor chemotherapy by means of an uniquely detailed analysis of cell population kinetics. The transplantable rat mammary adenocarcinoma 13762 (maintained in the PI's laboratory) responds to estrogen mustard (NSC 112259) by temporary regression and regrowth to a fatal conclusion. Estrogen mustard also damages the bone marrow and spleen. Consequently, the cell kinetics of the tumor, bone marrow, and spleen will be assessed during unhindered (pre-therapeutic) growth, and the quasi-linear phases of regression and regrowth. The kinetic analysis is based on determination of the DNA content distribution of H3TdR and/or C14TdR labeled nuclei on autoradiographs by means of an automated reflectance microspectrophotometer. The DNA content distribution of nuclei at sequential time points after pulse labeling will be analyzed by graphic and mathematical techniques to yield a description of cell population kinetics in terms of important function categories of cells and the rate of transfer of cells from one functional category to another. Specifically, the replication time and its component parts, the size of the replication and non-replication populations, the rate of transfer of cells between replicating and non-replicating populations, and rate of cell death will be determined. The analysis also quantitatively detects any populations of cells arrested in any of the phases of replication. This information should narrowly define the kinetics of the response of the host and the tumor to estrogen mustard. A second antitumor drug will be directed at kinetic weakness of the tumor vis a vis normal tissues produced by estrogen mustard, and the cell kinetics of the response to the combination therapy will be assessed. The results of this project will specify the kinetic mechanisms by which estrogen mustard, alone and in combination with a second antitumor vector, interferes with tumor growth.